Role of Human Aquaporin 5 In Colorectal Carcinogenesis

Abstract

While overexpression of several aquaporins (AQPs) has been reported in different types of human cancer, the role of AQPs in carcinogenesis has not been clearly defined. Here, by immunochemistry, we have found expression of AQP5 protein in 62.8% (59/94) of resected colon cancer tissue samples as well as association of AQP5 with liver metastasis. We then demonstrated that overexpression of human AQP5 (hAQP5) induces cell proliferation in colon cancer cells. Overexpression of wild-type hAQP5 increased proliferation and phosphorylation of extracellular signal-regulated kinase-1/2 in HCT116 colon cancer cells whereas these phenomena in hAQP5 mutants (N185D and S156A) were diminished, indicating that both membrane association and serine/threonine phosphorylation of AQP5 are required for proper function. Interestingly, overexpression of AQP1 and AQP3 showed no differences in extracellular signal-regulated kinase-1/2 phosphorylation, suggesting that AQP5, unlike AQP1, may be involved in signal transduction. Moreover, hAQP5-overexpressing cells showed an increase in retinoblastoma protein phosphorylation through the formation of a nuclear complex with cyclin D1 and CDK4. Small interfering RNA analysis confirmed that hAQP5 activates the Ras signaling pathway. These data not only describe the induction of hAQP5 expression during colorectal carcinogenesis but also provide a molecular mechanism for colon cancer development through the interaction of hAQP5 with the Ras/extracellular signal-regulated kinase/retinoblastoma protein signaling pathway, identifying hAQP5 as a novel therapeutic target.

Pleural lavage with distilled water during surgery for esophageal squamous cell carcinoma

“…As possible mechanisms, the strength of the cytoskeleton or the membrane, or the expression of the Cl -channels may differ among these ESCC cell lines. Further, overexpression of several types of aquaporins (AQP), transmembrane water channel proteins which play an important role in transcellular water movement, has been reported in different types of human cancer (24)(25)(26)(27). cAMP has been reported to up-regulate AQP5 expression in lung epithelial cells, hence increasing water permeability (28).…”

AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer

“…In particular, AQP5 expression in colon cancer tissues is associated with metastasis, suggesting that AQP5 overexpression plays a role in cancer progression (9). Ras signal transduction has been suggested to enhance cell proliferation in AQP5-overexpressed NIH3T3 cells (10).…”

Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells

“…10 AQP expression in tumors has also been proposed to be of diagnostic and prognostic value. 11,12 New evidence for the involvement of AQPs in cell…”